期刊
SCIENCE ADVANCES
卷 8, 期 13, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abj2667
关键词
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资金
- MEXT Q-LEAP [JPMXS0120330644]
- JST CREST [JPMJCR13L4, JPMJCR1656]
- JSPS KAKENHI [JP19H00919, JP20K15396, JP19KK0369, JP18H05155, JP18H01937, JP20H03217, JP20H05090, JP18H01186, JP16H06560]
- Interdisciplinary Computational Science Program in CCS, University of Tsukuba
- QST President's Strategic Grant (Exploratory Research)
- Intramural Research Program of the National Cancer Institute, NIH
Dynamic nuclear polarization (DNP) is an advanced technique that enhances the detection sensitivity of molecules in nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI). This study successfully developed a DNP-NMR molecular probe for in vivo detection of aminopeptidase N activity through precise structural investigation, calculation, biochemical assessment, and advanced molecular design.
Dynamic nuclear polarization (DNP) is a cutting-edge technique that markedly enhances the detection sensitivity of molecules using nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI). This methodology enables real-time imaging of dynamic metabolic status in vivo using MRI. To expand the targetable metabolic reactions, there is a demand for developing exogenous, i.e., artificially designed, DNP-NMR molecular probes; however, complying with the requirements of practical DNP-NMR molecular probes is challenging because of the lack of established design guidelines. Here, we report Ala-[1-C-13]Gly-d(2)-NMe2 as a DNP-NMR molecular probe for in vivo detection of aminopeptidase N activity. We developed this probe rationally through precise structural investigation, calculation, biochemical assessment, and advanced molecular design to achieve rapid and detectable responses to enzyme activity in vivo. With the fabricated probe, we successfully detected enzymatic activity in vivo. This report presents a comprehensive approach for the development of artificially derived, practical DNP-NMR molecular probes through structure-guided molecular design.
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